Preterm birth has an important impact on the neurodevelopmental and cognitive outcome of children at 9 years of age, being a risk factor for decreased regional cortical GM and WM even in preterm children with low risk for neurodevelopmental deficits.

There is increasing evidence about the presence of white matter damage in subjects with a history of premature birth, even in those classified as good outcome because of an apparently normal development. Although intellectual performance is within normal limits in premature children it is significantly decreased compared to paired controls. The purpose of this study was to investigate the relationship between a lower performance intelligence quotient and white matter damage in preterm adolescents. The sample comprised 44 adolescents (mean age+/-S.D.: 14.4+/-1.6 years) born before 32 weeks of gestational age and 43 term-born adolescents (14.5+/-2.1 years). Individual voxel-based morphometry analyses demonstrated that 35/44 (80%) preterm subjects had white matter abnormalities. The centrum semiovale and the posterior periventricular regions were the most frequently affected areas. Correlation analysis showed that in preterms the performance intelligence quotient correlated with the whole-brain white matter volume (r=0.32; P=0.036) but not with grey matter volume. Complementary analysis showed that low scores in the Digit Symbol subtest, a measure of processing speed, in the preterm group correlated with reductions in white matter concentration. These results suggest that white matter damage is highly common and that it persists until adolescence. Hence, diffuse white matter loss may be responsible for performance intelligence quotient and processing speed decrements in subjects with very preterm birth.

AimTo identify long-term effects of preterm birth and of periventricular leukomalacia (PVL) on cortical thickness (CTh). To study the relationship between CTh and cognitive-behavioral abnormalities.MethodsWe performed brain magnetic resonance imaging on 22 preterm children with PVL, 14 preterm children with no evidence of PVL and 22 full-term peers. T1-weighted images were analyzed with FreeSurfer software. All participants underwent cognitive and behavioral assessments by means of the Wechsler Intelligence Scales for Children-Fourth Edition (WISC-IV) and the Child Behavior Checklist (CBCL).ResultsWe did not find global CTh differences between the groups. However, a thinner cortex was found in left postcentral, supramarginal, and caudal middle rostral gyri in preterm children with no evidence of PVL than in the full-term controls, while PVL preterm children showed thicker cortex in right pericalcarine and left rostral middle frontal areas than in preterm children with no evidence of PVL. In the PVL group, internalizing and externalizing scores correlated mainly with CTh in frontal areas. Attentional scores were found to be higher in PVL and correlated with CTh increments in right frontal areas.InterpretationThe preterm group with no evidence of PVL, when compared with full-term children, showed evidence of a different pattern of regional thinning in the cortical gray matter. In turn, PVL preterm children exhibited atypical increases in CTh that may underlie their prevalent behavioral problems.

Periventricular leukomalacia (PVL) is the prototypic lesion in the encephalopathy of prematurity. Although PVL is identified by targeting cerebral white matter (WM), neuropathological and MRI studies document gray matter (GM) loss in cortical and subcortical structures. This study aimed to investigate the distribution of GM changes in children with a history of premature birth and PVL. Voxel-based morphometry was used to examine regional GM abnormalities in 22 children with a history of preterm birth and PVL. Preterms with PVL were compared with 22 terms and 14 preterms without PVL of similar GA and birth weight. GM and WM global volumetric volumes were found to decrease in comparison with both control groups. Regional GM volume abnormalities were also found: compared with their term peers, preterm children with PVL showed several regions of GM reduction. Moreover, PVL differed from preterms without PVL in the medial temporal lobe bilaterally, thalamus bilaterally, and caudate nuclei bilaterally. In addition, in our preterm sample with PVL, birth weight showed a statistical significant correlation with decreased GM regions. In conclusion, the voxel-based morphometry methodology revealed that PVL per se does involve GM reductions. (Pediatr Res 69: 554-560, 2011) P eriventricular leukomalacia (PVL) is the most prevalent type of brain injury in the preterm infant. As such, it is associated with long-lasting cognitive, behavioral, and sensorymotor impairments. PVL comprises two different patterns of white matter (WM) injury, focal, and diffuse, and the most frequently affected regions are those located contiguous to the external angles of the lateral ventricles (1). The focal component implies necrosis of WM tissue and, depending on its size, is termed cystic (macroscopic) PVL or noncystic (microscopic) PVL (2). Diffuse PVL, usually presenting as hypomyelination and ventriculomegaly, is due to premyelinating oligodendrocyte loss and subsequent microgliosis and astrogliosis (3).Although PVL characteristically affects cerebral WM (4), neuropathological studies in PVL samples have shown that gray matter (GM) lesions are frequently present in infants with PVL, indicating that WM injury is often accompanied by GM abnormalities in this preterm population (5,6). MRI studies have reported global cortical GM and thalamic volume reductions in preterm neonates with PVL (7-9).Voxel-based morphometry (VBM) is an automated procedure for quantifying GM and WM regional changes from a voxel-by-voxel analysis of MRI data (10). By using these procedures, we have previously found that premature adolescents without clinical WM lesions had WM reductions in several cortical and subcortical cerebral regions (11,12) and that prematures at low risk of neurodevelopmental disorders showed GM reductions, mainly involving the temporal lobe (13). However, this technique has yet to be used in the study of preterm children with PVL.The aims of this study were to investigate whether regional GM volume decreases were present in preterm chil...

Focal epilepsy can be conceptualized as a network disorder, and the functional epileptic network can be described as a complex system of multiple brain areas that interact dynamically to generate epileptic activity. However, we still do not fully understand the functional architecture of epileptic networks. We studied a cohort of 21 patients with extratemporal focal epilepsy. We used independent component analysis of functional magnetic resonance imaging (fMRI) data. In order to identify the epilepsy-related components, we examined the general linear model-derived electroencephalography-fMRI (EEG–fMRI) time courses associated with interictal epileptic activity as intrinsic hemodynamic epileptic biomarkers. Independent component analysis revealed components related to the epileptic time courses in all 21 patients. Each epilepsy-related component described a network of spatially distributed brain areas that corresponded to the specific epileptic network in each patient. We also provided evidence for the interaction between the epileptic activity generated at the epileptic network and the physiological resting state networks. Our findings suggest that independent component analysis, guided by EEG–fMRI epileptic time courses, have the potential to define the functional architecture of the epileptic network in a noninvasive way. These data could be useful in planning invasive EEG electrode placement, guiding surgical resections, and more effective therapeutic interventions.

INTRODUCTION:Thalamic abnormalities have been well documented in preterms with periventricular leukomalacia (PVL), although their contribution to long-term cognitive dysfunctions has not been thoroughly investigated. RESULTS: significant differences between groups were observed for global thalamic volume. Neuropsychological assessments showed that preterms with PVL scored within the normal range, although significantly below controls in the full intelligence quotient and the specific cognitive domains of processing speed and working memory. correlations of several thalamic regions with Working Memory Index and FIQ were found in the PVL group. Moreover, thalamic atrophy correlated with white-matter (WM) damage indexes (fractional anisotropy and radial diffusivity) assessed by diffusion tensor imaging. DISCUSSION: The findings suggest that thalamic damage is a common correlate of WM microstructural alterations and might be involved in the cognitive deficits seen in premature infants with PVL at school age. METHODS:We analyzed the impact of PVL-associated thalamic injury on cognitive status at school age and its correlation with WM integrity as measured by magnetic resonance imaging techniques. Thalamic volume and shape of 21 preterm children with PVL were compared with those of 11 preterm children of similar gestational age and birth weight with no evidence of focal WM abnormality.

Prematurity is associated with volumetric reductions in specific brain areas such as the hippocampus and with metabolic changes that can be detected by spectroscopy. Short echo time (35 ms) Proton magnetic resonance spectroscopy ( 1 H MRS) was performed to assess possible medial temporal lobe metabolic abnormalities in 21 adolescents with preterm birth (mean age: 14.8, SD: 1.3) compared with an age-matched control sample (mean age: 14.8, SD: 1.6).1 H MRS spectra were analyzed with linear combination model fitting, obtaining the absolute metabolite concentrations for Creatine (Cr), and myo-inositol (Ins). In addition, the following metabolite sums were measured: total Cho (glycerophospho-choline ϩ phosphocholine), total N-acetyl-aspartate ϩ N-acetyl-aspartylglutamate (NA), and total Glx (glutamate ϩ glutamine). A stereological analysis was performed to calculate hippocampal volume. Absolute Cr, and total NA values were decreased in the preterm group (p ϭ 0.016; p ϭ 0.002, respectively). The preterm also showed a hippocampal reduction (p Ͻ 0.0001). Significant relationships were found between gestational age and different metabolites and the hippocampal volume. Moreover, hippocampal volume correlated with brain metabolites in the whole sample. Results demonstrate that prematurity affects medial temporal lobe metabolites, and that the alteration is related to structural changes, suggesting that the cerebral changes persist until adolescence. (Pediatr Res 64: 572-577, 2008) I n vivo proton magnetic resonance spectroscopy ( 1 H MRS) is a neurochemical technique used to investigate specific brain metabolites, which can expand on the structural and functional information obtained by other neuroimaging techniques. Volumetric magnetic resonance imaging (MRI) analyses of subjects with history of preterm birth showed temporal gray matter (GM) reductions (1) and hippocampal changes that persist until the adolescence (2,3).A previous study reported that preterms evaluated at 40 gestational weeks showed increased N-acetyl-aspartate (NAA) compared with the concentrations at birth, and that the levels at the second examination did not differ from those of the full-term control group (4). These data suggest that metabolic decreases in the immature brain may normalize. In addition, a study in adolescents with preterm birth (Ͻ30 wk of gestation) found a NAA/Cho ϩ Creatine (Cr) reduction in the right temporal lobe in a subsample of preterms (n ϭ 9) compared with full-term subjects, suggesting a persistent deficit (5).No investigations to date have assessed abnormalities in the absolute metabolic concentrations by means of the userindependent frequency domain-fitting program LCModel in a healthy preterm sample at long-term or their relationship with hippocampal volumetric atrophy. The goal of our study was to determine whether single-voxel 1 H MRS is able to detect alterations in the medial temporal lobe region in adolescents with preterm birth and normal MRI. We hypothesized that volume reduction of the hippocampus could ...

Premature birth is associated with several brain dysfunctions including changes in the normal pattern of sulcal development. Previous studies on sulcal abnormalities were performed in subjects with perinatal brain complications. We selected a sample of preterm subjects with a low risk of neurodevelopmental abnormalities with the aim of investigating the effects of prematurity per se. Surface and maximum depth measures of four sulci that develop at different gestational ages were obtained using Anatomist/Brain Visa 3.0.2 software. The sulci measured were the olfactory sulcus (16 weeks), the parieto-occipital sulcus (22-23 weeks), the superior temporal sulcus (32 weeks) and the orbitofrontal sulcus (36-39 weeks). The sample comprised 17 low-risk preterms (mean gestational age: 32 weeks) and 16 full-term children who were matched for age at scan, gender, handedness and socio-cultural status. Analysis of surface variance showed a significant group effect (P<0.015), as well as an interaction between the type of sulcus and group (P<0.001). The superior temporal sulcus surface was inferior in the low-risk preterm group compared to controls. Our findings suggest that even without perinatal complications, premature birth affects sulcal morphology.